Background/Aims: Peritoneal fibrosis can lead to the discontinuation of continuous ambulatory peritoneal dialysis. The present study investigated the direct effect of aldosterone, which influences tissue fibrosis, and its cellular mechanism using cultured rat peritoneal mesothelial cells (RPMCs). Materials and Methods: The expression of aldosterone synthase (CYP11B2), mineralocorticoid receptors, 11β-hydroxysteroid dehydrogenase 2, serum- and glucocorticoid-inducible protein kinase 1 (SGK1) and connective tissue growth factor (CTGF) was evaluated using reverse transcriptase-polymerase chain reaction and Western blot. The ability of RPMCs to produce aldosterone was examined by enzyme immunoassay. Small interfering RNA of SGK1 was transfected to determine the role of SGK1. Results: CYP11B2, mineralocorticoid receptors and 11β-hydroxysteroid dehydrogenase 2 were expressed in RPMCs. The release of aldosterone from RPMCs into the culture medium was confirmed. Stimulation of RPMCs with the addition of aldosterone significantly increased SGK1 expression and phosphorylation and CTGF upregulation, and these effects were completely inhibited by the mineralocorticoid receptor antagonist spironolactone. SGK1 gene silencing abrogated aldosterone-induced CTGF expression. Conclusion: The local aldosterone system exists and acts directly as a profibrotic factor in the peritoneal mesothelium.

Keywords:
Peritoneal dialysis, Aldosterone, Fibrosis, Mesothelial cells
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© 2009 S. Karger AG, Basel
2009
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